Intermittent Fasting - A Primer ( Part 3 )

After having been successfully fasting for 20 hours on a daily basis, as outlined in part 2, hopefully, everything is going as you intended, and you are seeing and feeling results. At the very least I hope that you are enjoying your liberation from having to eat in accordance with a schedule set by societal convention, rather than in accordance with your goals and priorities. Nevertheless, in spite of your successes, you may be wondering, can we do better?

We have already established that an inter-meal interval of some 20 odd hours is not detrimental to health, quite the opposite, overall health and body composition seem to benefit from such an eating pattern. So, what would happen if we were to increase the interval between meals even further? How far is it prudent to go before we cross the dividing line between fasting and starvation? What would be the impact of doubling the inter-meal interval to 40h? We are actually rather fortunate with respect to answering the question, since every study performed on the effects of starvation on the human metabolism will have necessarily started out with a 40 hour fast. The only real complication will be due to the frequency of data collection, as many studies tend to focus their data collection on the latter phases. Let's see what we can find.

The Impact of the 40 hour fast

Growth Hormone

Growth hormone is very interesting due to the role that it plays with respect to nutrient availability as energy substrates. Ingesting both glucose and FFAs suppresses GH release, while certain amino acids tend to stimulate secretion. For the purposes of fasting, when exogenous sources of glucose and FFAs fall, GH levels rise to mobilize internal stores of both of these energy substrates. That is, GH promotes increased production of glucose by the liver, increases the breakdown of adipose fat tissue, as well as promoting nitrogen conservation ( protein tissues are spared ). As the bulk of growth hormone tends to be secreted at night, if there were any effect of fasting on GH, we would most likely like to include a fasted night time period in our approach. It turns out that a two day fast results in a five fold increase in the 24-h GH production rate. Essentially, what we're trying to do by extending the fast is to take advantage of the GH secretory burst that happens during the night, 24 hours or so into the fast, indicated with a red arrow in the graph below:

Free fatty acids

Given that GH production rate increases five fold, we would expect, due to the lipolytic effects of the hormone, to see an increase in the circulating level of FFAs. As you can see from the table below, this is precisely what we observe. Around 32 hours into a fast, the FFA acid concentration in the blood is 3x higher than 8 hours into the fast ( ie an overnight / sleep fast ). 56 hours into the fast, that number has only increased by a further 20% suggesting that we are approaching a limit. The biggest bang for our buck seems therefore to be around 32+ hours. Given that we have all of these FFAs in the bloodstream 32 hours into a fast, it seems reasonable that we need to give the body a chance to oxidize the fats. We achieve this by keeping the fast going. It would undo all of our hard work were we to eat at this point and have the FFAs simply be reabsorbed by adipose tissue.

The fact that FFA release peaks after two days of fasting is confirmed by the results in another study shown below. Due to the way that these authors labelled their graph, day two of the graph is represented by the line segment between the axis markers labelled "Day 2" and "Day 3".

We should also pay close attention to the acetoacetate (AA) and beta hydroxybutyrate (BOH) on this graph. Both AA and BOH are ketone bodies produced by hepatic FFA oxidation, which means that, again, as expected, we're burning fat to provide an alternative energy substrate (ketones) for the brain and heart to use in lieu of glucose. Speaking of which, looking at the glucose levels on this graph, we see that during the first day of the fast, the liver can sustain nominal levels from its glycogen stores, but starting with the second day, we start a downward trend. This is significant, because at some point, the body will be forced to enter proteolysis, breaking down protein containing tissues, to provide inputs for gluconeogenesis thereby sacrificing lean mass for brain sustaining glucose. We wish to avoid this state, which will practically limit our fasting to a couple of days at most.

Cortisol

We expect that Cortisol will trend upward over the course of a fast due to its proteolytic effects - increasing the breakdown of protein to make gluconeogenic substrates like alanine available for conversion to glucose. As the liver exhausts its supply of glycogen, generally within the first day of fasting, available blood glucose levels drop, and it becomes increasingly important to have the proteolytic effects of cortisol kick in. As expected, in the total fasting time graph above, we can see that Cortisol, over time, shows a slight upward trend, but, with respect to the levels at hours 8 and 36, they are roughly equal, suggesting that a fast of this duration is not a metabolic stress inducer, and does not require excessive conversion of protein from tissues as an energy substrate.

Insulin

For the most part, there is not much to say here. From looking at our graph, we can see that over the course of a fast, insulin levels progressively drop. However, there is a very interesting rebound in insulin levels at the end of the fast, at 84 hours into the study, and here insulin levels rebound to levels seen 16 hours into the fast, but based solely on the anticipation of food!

So, what does all of this mean?

Fundamentally, if you are really concerned with body recomposition, that ultimately translates into burning adipose FFAs to reveal your underlying musculature. In terms of accelerated FFA oxidation, there is no substitute for a multi day fast. The first day of any fast serves to draw down liver glycogen stores. The subsequent days are spent oxidizing FFAs for energy. I would not advise going beyond 40 - 48 hours as you risk entering into the proteolytic zone.

My personal experience, as well as that of others that have done this, is that the second day of a fast is generally easier than the first. I speculate that this is because insulin levels consistently drop as the fast progresses, and accordingly, perceived hunger drops as well. If you have habituated yourself to eating one meal per day in the evening, then a 40 hour fast actually entails merely skipping your one meal. For my part, I do this on a weekly basis.

I think I will leave you with this for the time being. There is a lot to digest here, maybe too much.

I did my 1st 40+hr fast last week. Couldn't believe how easy the last 15hrs was. When it was time to break the fast I wasn't even really hungry, could have gone on longer. After ready the above it's a good thin I didn't.

Thanks pklopp. Gonna give this a try. However, what would you suggest for training during this 40h fast? Should I skip training (just move it to another day), go lighter on the weights, lift normally and hope I don't bonk or just take some BCAAs if I do train?

Just wondering.

People too weak to follow their own dreams will always try to discourage others.

pklopp, just wanted to say thank you for the great information. How do you feel about taking bcaas even when not training during the fast. Do you think it would mess up the normal process of fasting and how your body responds to it?

Timely information. I am convinced that some sort of fasting protocol is important to maintaining good body composition and optimal health. I have never been obese or really heavy but I always want to be leaner than I am most of the time. I eat well, just too much and struggle not.

Today I did a dinner to dinner 6pm to 5pm today fast and it was frankly much more pleasant than having to try and not eat. I ate a large dinner (maybe about 20% more than normal if that). I was able to do two light workouts with no issue and never sat down the entire day. I will continue this until I get to my desired weight (about 20 pounds). I will likely do a 2 day fast each week since this post points to some great potential benefits.

We expect that Cortisol will trend upward over the course of a fast due to its proteolytic effects - increasing the breakdown of protein to make gluconeogenic substrates like alanine available for conversion to glucose. As the liver exhausts its supply of glycogen, generally within the first day of fasting, available blood glucose levels drop, and it becomes increasingly important to have the proteolytic effects of cortisol kick in. As expected, in the total fasting time graph above, we can see that Cortisol, over time, shows a slight upward trend, but, with respect to the levels at hours 8 and 36, they are roughly equal, suggesting that a fast of this duration is not a metabolic stress inducer, and does not require excessive conversion of protein from tissues as an energy substrate.

You say that the slight upward trend in cortisol is not too proteolytic, but it is somewhat so. So are GH and cortisol kind of antagonistic to each other? In that the former encourages liver glucose production and the use of stored adipose tissue. Or is it that cortisol can encourage gluconeogenesis so that GH can then stimulate the liver to make glucose from those substrates?

Is the slight increase in cortisol anything to be worried about for those concerned about the cortisol-belly fat connection? Or, if the abdomen is the place of stored subcutaneous fat, would the benefits of longer fasts outweigh the potential negatives?

A number of you have asked about how to go about breaking the fast, whether it mattered, and if so, what macronutrients, ratios, etc. would be advisable?

The quick and confusing answer is that it matters and it doesn't.

The reason it matters is that unless you have been eating this way for quite some time, there will be a period of adjustment during which if you eat particularly rich foods to break your fast, these may cause some gastric upset. For me, the only time that I experienced problems was when I broke my fast with a particularly fatty meal. I overdosed on cheese ... once ... haven't done it since. I think eggs make a pretty good breakfast and break fast. High in protein, high in good fats, easy to prepare, quite gentle on the stomach. I always have some vegetables, mostly salads Personally, I don't particularly care for carbohydrates, and I don't seek them out when breaking my fast, but you can probably get away with them here.

The reason it doesn't matter is that your body needs food, and will be plenty happy to get it irrespective of its ultimate form. From an evolutionary perspective, an organism that is living in an energy uncertain environment ( hence the fast, due to irregular availability of food ) but then requires a specific nutritional makeup for any food that it should happen to find is one dead organism. This is tantamount to the man crawling through the desert, finding an oasis, dragging himself up to it only to ask "Do you have any sparkling water?" We cannot rule out such potential behaviour, but we can predict that it runs contrary to the survival of the organism.

I understand that the underlying motivation behind the question is an attempt to wring every last ounce of benefit from this process. This is commendable, but I think it is certainly a case of premature optimization. Get the basics down first, then tweak for that final 1%.